Employing Holmes on a case cant always give happy endings. Sometimes, what he uncovers is tragedy that cannot be repaired.
- The Cardboard Boxs case may be the most tragic one in the bunch: a husband and wifes marriage is wrecked by a jealous sister who tried to force herself on the husband and was rejected. The husband kills his wife and her lover, but is so broken with guilt over what happened that he confesses all and welcomes execution. Even the wife's sister doesn't get away unscathed, since she's so horrified by the guilt on learning that all her scheming has resulted in the wife's horrible murder that she has a mental breakdown. Holmes at the end of the case somberly ponders the existence of life, and whether there can be any salvation for the pitiful.
- The Five Orange Pips has Holmes client John Openshaw get murdered by the Ku Klux Klan. The police didnt take the threats to his life seriously, and when he visits Holmes (which Holmes says he should have done before) he is advised to be careful, a warning that comes too late to save him. Holmes is briefly devastated at the death he couldnt prevent in time.
- The Adventure of the Dancing Men has Holmes Late to the Tragedy. He deciphers the titular code, but is too late to prevent the death of poor Hilton Cubit and his wife's Attempted Suicide.
- The Veiled Lodger is less a mystery than a tragedy; of a young artiste married to an abusive husband, whose murder plot to free herself succeeded, but at the cost of her face. She was so maimed that she spent the rest of her life alone, and even had thoughts of suicide before her meeting with Holmes.
- The Speckled Band tells the tale of Helen Stoner, trapped by an abusive stepfather looking to gain her inheritance through murderous intent and has already slain her sister.
- Furthermore, this case opens with Watson narrating that the case can be disclosed because Stoner has died. She was free from peril, but led a short life. Who knows if she never really got over the incident?
- The Missing Three-Quarter kicked off because a rich rugby players secret wife (they were married secretly because hed have otherwise lost his inheritance) became fatally ill. Holmes tracks down the player to find him in tears at his wifes deathbed.
- The Three Garridebs ends with Nathan Garrideb, who was deceived into thinking his unusual name would entitle him to a fortune, going mad on the reveal of the scam, and spending the rest of his life in a nursing home.
- In "The Devil's Foot" it turns out that Dr. Sterndale was in love with Brenda Tregennis (one of the initial murder victims) for years, and vice versa, but they couldn't marry because Sterndale was unable to divorce his current wife. When he learns that Brenda not only died in agony along with her brothers being driven insane, but the murderer used a poison stolen from him, he tracks him down and kills him using the same poison...but is left devastated at Brenda's death, and with nothing left now except his work in Africa. Holmes and Watson are moved and let him depart.